(627g) Controlling Cell Adhesion and Migration through Ligand Presentation

Cell attachment and migration are key steps during normal processes such as morphogenesis and immune surveillance, but are also intimately involved in pathologies such as tumor growth and metastasis. Recent studies have called attention to the nature of the cell-material interface and its poorly understood role in both physiological and pathological contexts. Because cells sense and respond to multiple environmental cues, the biochemical and biophysical presentation of ligands can regulate a variety of cellular characteristics such as adhesion, migration, differentiation, and survival.

We report the development of a dynamic polymeric bilayer to examine and potentially control receptor-ligand interactions. The self-assembly of amphiphilic block copolymers (1,2-polybutadiene-b-poly(ethylene glycol): PBd-b-PEG) at the air-water interface allows us to control the presentation of ligands at the surface as well as polymer orientation (e.g., brush or mushroom). The hydrophobic block PBd provides a means for controlling surface diffusion by cross-linking while the hydrophilic block PEG is biocompatible and resistant to protein adsorption. Transfer of our interfacial monolayers onto a substrate via a Langmuir-Blodgett/ Langmuir-Schaefer (LB/LS) technique results in biomimetic surfaces with a dynamic character, because lateral diffusion of ligands is preserved. This type of film structure and behavior closely resembles that of lipid membranes, with polymer films having increased robustness and dynamic range. Biofunctionalization of this block copolymer with the tripeptide RGD allows specific interaction with cellular integrin receptors, while mixing with unmodified material of similar or varied molecular weights will control effective ligand concentration and accessibility.

The tunability and characterization of our surfaces by ellipsometry, atomic force microscopy, dynamic contact angle, and fluorescence methods will be discussed. Preliminary results on cell adhesion will also be presented. These surfaces will initially be used to study the mechanism of invasive cancer cell adhesion and migration with a focus towards understanding the metastatic ability of cancer cells.